Cerebral proliferative angiopathy: A rare clinical entity with peculiar angiographic features.

Case Report

An 18-year-old male presented with episodes of generalized tonic clonic seizures for 1 year. His compliance to treatment was not very good leading to poor seizure control. There was neither any history of headache, vomiting or any stroke like episode nor his neurological examination was suggestive of any focal neurological deficit.

Initially magnetic resonance imaging brain was done elsewhere which revealed large left frontal parasagittal arteriovenous malformation (AVM) [Figure 1]. Subsequently cerebral digital subtraction angiography (DSA) was done at our center. DSA showed diffuse proliferative angiopathic changes suggestive of cerebral proliferative angiopathy (CPA) [Figure 2].

Figure 1

Magnetic resonance imaging brain axial, coronal and sagittal T2-weighted images showing multiple flow voids in left frontal parasagittal region with multiple dilated veins draining into superior sagittal sinus suggestive of arteriovenous malformation

Figure 2

Cerebral digital subtraction angiography left internal carotid artery injection (a) showing diffuse proliferative angiogenesis with feeders supplied from branches of left anterior cerebral artery and left middle cerebral artery. (b) The venous drainage is through deep venous system and superficial venous system into superior sagittal sinus. (c) Left external carotid artery injection shows no drainage

Patient was managed conservatively with antiepileptic drugs with strict adherence to compliance and was seizure free and doing well until he was lost to follow-up 1 month later.

Discussion

Our patient was having an atypical angiopathy which is distinct from other brain AVMs[1] and is relatively rare comprising 3.4% of all brain AVMs in one series.[2]

Only few cases of this rare clinical entity have been described in the world literature till now, after the series of Lasjaunias et al.[2] The salient issues of cerebral proliferative angiopathy (CPA) which helps to discern it from “classical” brain AVMs[1] are: The absence of dominant feeders or flow-related aneurysms, the presence of proximal stenosis on the feeding arteries, the extensive transdural supply to both healthy and pathological tissues, the large size (which might be lobar or even hemispheric), the presence of capillary angioectasia and the only moderately enlarged veins (compared with the size of the nidus).

In our patient cerebral DSA [Figure 2] showed diffuse angiogenesis, absence of a well-formed nidus and early venous phase suggestive of fast capillary transit favoring the diagnosis of CPA.

This entity has a significantly different clinical presentation and clinical course compared with classical brain AVMs. Patients (typically, young females 2:1) usually do not present with an acute neurological deficit or hemorrhage but more commonly with epileptic manifestations, headaches and progressive neurological deficits, however, when they do bleed, the risk of recurrent hemorrhage seems to be higher.[2] Similar was our observation in that in spite of there being such a large AVM, it never lead to hemorrhage or any focal neurological deficit but only served as an epileptogenic focus. Other particular features are the high rate of stroke-like symptoms, TIAs (transient ischemic attacks), and neurological defects not owing to a hemorrhage that suit the assumption that CPA is a disease related to ischemia rather than hemorrhage. Seizures and disabling headaches also occur in the CPA population more than the AVM population.[2]

Treatment indications in the series of Lasjaunias et al,[2] were set very strictly and were confined to hemorrhage, identifiable fragile angioarchitecture (such as intranidal aneurysmal ectasias), uncontrollable seizures and disabling headaches. Surgery, radiosurgery and large non-targeted embolization carry the risk of permanent neurological deficit attributable to the interspersed normal neural tissue. These kinds of treatment should therefore be reserved to patients with otherwise intractable headaches and epilepsy.

Because one of the major pathomechanisms of this disease is ischemia (which in itself is probably multifactorial owing to incompetent angiogenesis, “steal” phenomena, arterial stenosis, and capillary wall involvement) a therapy that enhances cortical blood supply can be indicated. Apart from targeted embolization, other treatment options are synangiogenesis and calvarial burr holes both of which act by increasing cortical blood supply but there is not sufficient data to establish their utility as a primary treatment modality.[23] Similar to Moyamoya-like diseases these burr holes increase the cortical blood supply by recruiting additional dural blood supply.

However, in patients presenting with hemorrhage, endovascular treatment should be performed, aiming at “fragile” areas that may be identified during angiography.[4] Our patient, neither presented with hemorrhage nor was there was any fragile area or any intranidal aneurysm identifiable on DSA, making target embolization useless and leaving us with conservative treatment as the best possible option.

It is important to recognize this rare entity of CPA from the various features as described above. Treatment of this disease is challenging and management of such patients is best done at centers with expertise in cerebrovascular diseases.